Method and apparatus for the dilution and division of a stream of samples for continuous analysis



7 April 1; 1969 w. J. SMYTHE METHOD AND APPARATUS FOR THE DILUTION ANDDIVISION FIG.2

OF A STREAM 0F SAMPLES FOR CONTINUOUS ANALYSIS Filed Oct. 2, 1967INVENTOR.

WILLIAM J. SMYTHE ATTORNEY METHOD AND APPARATUS FOR THE DILUTION ANDDIVISION OF A STREAM OF SAMPLES FOR CONTINUOUS ANALYSIS William J.Smythe, Rye, N.Y., assignor to Technicon Corporation, Ardsley, N.Y., acorporation of New York Filed Oct. 2, 1967, Ser. No. 672,055 Int. Cl.G01n 1/28 US. Cl. 73-423 9 Claims ABSTRACT OF THE DISCLOSURE A systemfor prediluting a flowing stream of samples and for dividing the dilutedstream into a plurality of quotient streams includes a peristaltic typepump coupled to an olf-take tube for aspirating samples, from respectivecontainers, interspersed with relatively large gas segments. A valvedpump tube periodically adds relatively small gas segments to a separatestream of diluent and this segmentized diluent stream is added to thesample stream and is mixed therewith. Each of the relatively small gassegments is withdrawn and the debubbled, mixed, sum stream is dividedinto a plurality of quotient streams, each having a portion of eachsample and each relatively large gas segment.

BACKGROUND OF THE INVENTION Field of the invention This inventionrelates to the automatic, continuous analysis of a flowing stream ofliquids, and, more particularly, to a system for continuously dividingthe initial sample stream into a plurality of quotient streams, some ofwhich are diluted.

Prior art Systems for the automatic, continuous analysis of liquids arewell known. Such a system is shown in US. Patent No. 2,797,149, issuedto L. T. Skeggs on June 25, 1957. The analysis system is fed sequentialsamples as a flowing stream by means of an off-take device whichaspirates liquid from each of a plurality of sample containers, whichare sequentially presented thereto by a sampler assembly, such as isshown in U.S. Patent No. 2,879,141, issued to L. T. Skeggs on Mar. 24,1959. More recently, systems have become known wherein the initialstream of samples is divided into a plurality of quotient streams, eachcontaining a fractional portion of each sample from the initial stream.Each quotient stream is then analyzed, and the results are recorded incorrelation automatically. Such a system is shown in US. Patent No.3,241,432, issued to L. T. Skeggs et al. on Mar. 22, 1966. The samplermay be as shown in US. Patent No. 3,230,776, issued to I. Isreeli et al.on Jan. 25, 1966, which provides a segment of wash liquid betweensuccessive samples.

Much of this analytical work is in the clinical field, and is especiallydirected to the analysis of blood samples for different constituentsthereof. The number of constituents being limited by the number ofquotient streams provided. Present commercial systems may provideanalyses of 60 samples per hour for 12 constituents of each sample.

I have found that it is advantageous to dilute the initial stream duringthe division of the stream into the quotient streams. This provides athreefold benefit. Firstly, it ensures that each sample quotient is ofconveniently large volume for processing. Secondly, it minimizes thepossibility of clogging of the small diameter conduits by the non-liquidmaterial carried in the blood sample.

3,435,684 Patented Apr. 1, 1969 Thirdly, it permits a reduction in thesensitivity of certain colorimetric reactions, so that the opticaldensity thereof is kept within the substantially linear range of thedetector-recorder subsystem.

SUMMARY OF THE INVENTION The principle of this invention is comprised ina system for uniformly diluting a flowing stream of sequential liquidsamples in which successive liquid samples are spaced apart by a gassegment, and for dividing this diluting stream into a plurality ofquotient streams. The system includes means for transmitting through aconduit an initial stream of sequential liquid samples, each spaced fromthe succeeding sample by a relatively large gas segment; means forcontinuously adding relatively small, spaced apart gas segments, whichare just large enough to occlude the conduit, to a stream of diluent andadding this combined stream to the initial stream; means for intramixingthe liquid segments in the stream of sample plus diluent; means forcontinuously removing a portion of the mixed stream at a volumetric ratejust great enough to remove each of the relatively small gas segmentswhile leaving at least enough of each of the relatively large gassegments to occlude the conduit; and means for dividing the remainingportion of the stream into a plurality of quotient streams for analysis,each quotient stream containing a portion of the relatively large gassegment adequate to occlude the conduit.

BRIEF DESCRIPTION OF THE DRAWING FIGURE 1 is a diagram of a flow systemembodying this invention; and

FIGURE 2 is a perspective view of a detail of the flow system.

THE PREFERRED EMBODIMENT The embodiment shown in FIGURE 1 includes asample supply apparatus 10, such as is shown in US. Patent No. 3,230,776supra, having a carrier 12 supporting a plurality of containers 14 forliquid samples, a container 16 for a wash liquid, and an oif-take tube18 which has an inlet which is inserted sequentially into each of saidsample containers, and between successive containers is inserted intothe wash container 16. The outlet end of the off-take tube 18 is coupledby a conduit 20 to a junction 22 having an inlet 24 and five outlets 26,28, 30, 32 and 34. Pump tubes 36, 38, 40 and 42 are respectivelyconnected to the outlets 26, 28, 30 and 32. These pump tubes aredisposed in a peristaltic type pump P, such as is shown in US. PatentNo. 3,306,229, which includes a platen and a plurality of rollers forprogressively advancing fluids through the pump tubes. This pump alsohas an air bar 44 for occluding one or more pump tubes and forintermittently and periodically releasing such pump tubes, providing avalving function.

The outlet 34 is conected to one end of a pump tube 46, whose other endis coupled to one inlet 48 of a junction 50 having an additional inlet52 and an outlet 54. A pump tube 56 has its inlet end coupled to asource of relatively inert gas G, such as the atmosphere, and its outletcoupled to an inlet 58 of a junction 60 having another inlet 62 and anoutlet 64. The pump tube 56 is so disposed in the pump as to be occludedby the air bar 44. A pump tube 66 has its inlet end coupled to a sourceof diluent D, such as water, and its outlet coupled to the inlet 62. Theoutlet 64 is coupled by a conduit 67 to the inlet 52. The outlet 54 iscoupled to the inlet of a mixing coil 68 whose outlet is coupled by aconduit 69 to the inlet 70 of a junction 72.

The junction 72 has two outlets 74 and 76. A pump tube 78 has its inletend coupled to the outlet 74. The outlet 76 is coupled to a plurality ofserially connected junctions 80, 82, 84, 86, 88, 90, 92, and 94, eachhaving an outlet coupled to a respective one of a plurality of pumptubes 98, 100, 102, 104, 106, 108, 110 and 112. Each of these tubes 98,100, 102, 104, 106, 108, 110 and 112 is coupled to an inlet of arespective junction 116, 118, 120, 122, 124, 126, 128 and 130.Similarly, each of the pump tubes 36, 38, 40 and 42 is coupled to aninlet of a respective junction 134, 136, 138 and 140.

As shown in U.S. Patent No. 3,241,432, supra, junc tions 134, 136, 138and 140 respectively form parts of analysis manifolds, for thedetermination of respective constituents, which do require predilutionof the sample, according to this invention, for example, albumin, totalprotein, chloride, carbon dioxide, sodium, potassium, glucose, andblood-urea-nitrogen.

The off-take tube is disposed in a sample container 14 and withdrawssample liquid at a predetermined rate, such as 2 ml./sec. After aninterval of time the off-take tube is withdrawn and, advantageously,disposed in a container of wash liquid, such as water. During the timeof travel between containers the off-take tube aspirates a volume ofair, such as 0.17 ml. After an interval of time the off-take tube iswithdrawn and disposed into the next sample container, aspirating asimilar volume of air. Thus, successive samples are separated by atleast a large bubble of air, if the wash liquid is omitted, and by twobubbles and a wash liquid segment, if the wash liquid is included. Aportion of this initial flowing stream of sample segments, air bubbles,and wash segments from the off-take tube is divided oil at each of theoutlets 26, 28, 30 and 32 to form four respective quotient streams. Eachof these quotients withdraws a portion of the volume of the large airbubble, which may total a loss of 0.07 ml., leaving an air bubblebetween segments of 0.1 ml. flowing through the pump tube 46 to thejunction 50. The air bar 44 periodically releases small volumes of air,such as 0.008 ml. 30 times a minute into the stream of diluent flowingthrough the pump tube 66 to the junction 60. These small volumes of airare adequate to occlude the conduit 66, and to occlude the conduit ofthe mixing coil 68 after addition to the sample stream at the junction50. These small bubbles serve to compartmentalize the segments of sampleand added thereto diluent, and insure uniform mixing of this sum stream,as taught in U.S. Patent No. 3,306,229, supra.

The junction 72 has an inlet arm and a lower outlet arm which arerelatively horizontal and an upper outlet arm which is upwardlydirected, and has a volume A at the intersection of the arms which isgreater than the volume of the smaller air bubbles, such as .01 ml. Thusthe entire volume of these small bubbles is taken off through theupwardly directed outlet arm and the pump tube 78 to waste. However, atthis point, the sample stream has been uniformly diluted. A portion ofthe diluted stream is now removed at each of the subsequent junctions 80et seq. to provide quotient sample streams. Each of these junctions hasa relatively small volume, similar to junction 72, such as .01 ml. sothat a portion of the large air bubble (now .09 ml.) is available foreach quotient stream. This portion of the air bubble suffices to providea cleansing action through the pump tubes to the junctions 116 through130. At these junctions a suitable diluent, and supply of small airbubbles is added to each quotient stream, as taught in U.S. Patent No.3,241,432, supra.

It will be appreciated, that if necessary, the wash liquid segment, willprovide a visual indication of the demarcation between segments ofsuccessive samples.

While there has been shown and described a presently preferredembodiment of the invention, it will be understood that the inventionmay be embodied otherwise than as herein specifically illustrated ordescribed and that in the illustrated embodiment certain changes in thedetails of construction and in the form and arrangement of parts may bemade without departing from the underlying idea or principles of theinvention. Accordingly, the invention is not limited to the priorconstruction shown or described herein.

What is claimed is:

1. A method of preparation for analysis of a plurality of liquid sampleswith respect to a number of different constituents present in eachsample comprising:

sequentially transmitting said samples through a conduit, each samplebeing spaced from the preceding sample by a relatively large gassegment, to form an initial stream of sequential samples;

continuously adding to said initial stream a stream of diluent anduniformily spaced apart relatively small gas segments to form a sumstream;

continuously intramixing the sum stream of sample and diluent;

continuously withdrawing said relatively small gas segments but not allof said relatively large gas segments from said sum stream; and

continuously dividing said sum stream into a plurality of quotientsample streams.

2. A method according to claim 1 wherein:

said relatively small gas segments are uniformly, in-

termittently added to a stream of diluent, which is then continuouslyadded to said initial sample stream.

3. A method according to claim 1 further including:

continuously adding to each quotient stream a respective stream ofreagent and uniformly spaced apart relatively small gas segments.

4. A method according to claim 1 wherein the division of said sum streaminto a plurality of quotient streams includes a portion of each dilutedsample segment and a porton of each relatively large gas se ment foreach quotient stream.

5. Apparatus for the preparation for analysis of a plurality of liquidsamples with respect to a number of different constituents present ineach sample comprising:

supply means coupled to a junction for transmitting the samplessequentially through the junction, each sample being spaced from thepreceding sample by a relatively large gas segment, to form an initialstream of sequential samples;

additional supply means coupled to the junction for continuously addingto said initial stream a stream of diluent and uniformily spaced apartrelatively small gas segments to form a sum stream; mixing means coupledto said junction for continuously intramixing said sum stream of sampleand diluent;

debubbling means coupled to and downstream of said mixing means having acapacity adequate for withdrawing each of said relatively small gassegments from said intramixed sum stream, yet inadequate for withdrawingmost of each of said relatively large gas segments; and

dividing means coupled to and downstream of said debubbling means fordividing said intramixed, debubbled sum streams into a plurality ofquotient streams, each quotient stream including a portion of eachdiluted sample segment and a portion of each relatively large gassegment.

6. Apparatus according to claim 5 wherein:

said supply means includes a plurality of sample containers;

a pump means; and

an off-take means having an off-take tube which is coupled to said pumpmeans and insertable sequentially in each of said sample containers;

whereby said off-take tube aspirates sample when disposed in a samplecontainer and aspirates air When withdrawn from the sample containers.

7. Apparatus according to claim 6 wherein:

said supply means further includes a wash liquid container into whichsaid off-take tube is inserted between insertions in successive samplecontainers;

whereby said initial stream includes sequences of sample liquid, arelatively large air segment, wash liquid, and a relatively large airsegment.

8. Apparatus according to claim 5 wherein said mixing means comprises ahelical coil having a horizontal axis.

9. Apparatus according to claim 5 wherein said additional supply meansprovides said relatively small gas segments with a predetermined volume;

said debubbling means comprises a junction having a substantiallyhorizontal inlet and outlet and an additional, upwardly directed outletwhich is coupled to a pump means, and a volume contained between saidinlet and outlets at least equal to said predetermined volume of saidrelatively small gas segments.

References Cited UNITED STATES PATENTS 3,020,130 2/ 1962 Ferrari 23-2303,109,713 11/1963 Ferrari et a1 23--253 3,134,263 5/1964 De Jong 7342310 3,241,432 3/1966 Skeggs et a1 23-230 XR LOUIS R. PRINCE, PrimaryExaminer.

HARRY C. POST, Assistant Examiner.

